Potentiometric sensors comprise a measuring half-cell and a reference half-cell. The measuring half-cell includes a sensitive element, which is frequently embodied as a measuring membrane, on which a potential occurs, dependent on the measured variable. Used as reference half-cell can be, for example, a reference electrode of second type known per se, e.g. a silver/silver chloride, reference electrode, which provides a stable reference potential independent of the measured variable. The determining of the measured variable occurs based on the registering of a potential difference occurring between the measuring half-cell and the reference half-cell in contact with the measured medium. Examples of such potentiometric sensors are so-called ion-selective electrodes (ISEs).
A special case of an ion-selective electrode for determining the pH-value of a liquid is the glass electrode for pH-measurements. The glass electrode includes a housing, in which a measuring half-cell chamber is formed, which is sealed on an end by a pH-sensitive glass membrane. Accommodated in the measuring half-cell chamber is an inner electrolyte, which, as a rule, comprises a pH buffer system. The glass membrane thus contacts the internal electrolyte with its inner surface facing the measuring half-cell chamber. For performing pH-measurements, the outer surface of the glass membrane facing away from the measuring half-cell chamber is brought in contact with a measured medium. In contact with a water containing medium, the glass membrane forms a gel layer. In such case, there occurs on the interface between the membrane glass and the aqueous medium a dissociation, in the case of which alkali ions of the glass are replaced by protons from the aqueous medium, so that a large number of hydroxyl groups are formed in the gel layer. In measurement operation of the electrode, this occurs both on the inner surface contacting the inner electrolyte as well as also on the outer surface of the membrane contacting the measured medium. Depending on the pH-value of the measured medium, H+ ions diffuse out from the gel layer or into the gel layer. Since the inner electrolyte has a constant pH-value, there thus results across the membrane a potential difference dependent on the pH-value of the measured medium. For achieving a stable potential on the glass surface and for assuring a fast response, i.e. a short time span between immersion of the measuring membrane in the measured medium and the reaching of a value of the membrane potential fluctuating only within a predetermined error/tolerance range, the gel layer must be completely formed. After a drying out of, or other damage to, the gel layer, this response time can lengthen significantly, until even a number of hours can be required for reaching a constant, measured value.
A reference electrode of second type, such as the silver/silver-chloride electrode, includes, formed in a housing, a reference half-cell chamber, which contains a defined electrolyte solution. This inner electrolyte must contact the measured medium, in order to be able to perform a measurement. Such contact is via a liquid junction, which can be produced, for example, by a passageway through the housing wall, by a porous diaphragm or by a gap. Extending into the inner electrolyte is a potential sensing element. The potential of the reference electrode is defined by the reference electrolyte and the potential sensing element. In the case of a silver/silver-chloride electrode, the inner electrolyte is, for example, an aqueous solution of high chloride concentration, as a rule, a 3 molar, or saturated, KCl solution, and the potential sensing element is a chlorided silver wire.
Since the potential of the reference half-cell is essentially pH-value independent and can be assumed to be constant as a function of time, the potential difference registerable between a potential sensing element extending into the inner electrolyte of the measuring half-cell and the potential sensing element of the reference half-cell by means of a measurement circuit is a measure for the potential difference between the inner surface of the measuring membrane and the outer surface of the measuring membrane dependent on the pH-value of the measured medium, and, thus, a measure for the pH-value of the measured liquid.
Such potentiometric sensors can be embodied as a measuring chain with two separated, in each case, rod-shaped, housings for measuring- and reference half-cells. Frequently, the two half-cells are, however, combined into a single-rod measuring chain, or combination electrode, which has a single housing, in which are formed two chambers separated from one another, wherein one chamber serves as measuring half-cell chamber and the other as reference half-cell chamber.
Both half-cells should, not only during measurement operation, but also during storage, be sitting in a liquid, for example, in a buffer solution or in a salt solution. In the case of dry storage of the sensor, it is possible, on the one hand, that the inner electrolyte of the reference half-cell can leak out through the liquid junction, or dry out, while, on the other hand, the gel layer of the measuring half-cell can dry out. In order to be able to get a dry stored, potentiometric pH-sensor back in operation, the measuring half-cell must be placed at least 12 hours in a water containing buffer- or electrolyte solution, in order to build anew a gel layer formed sufficiently for assuring a fast response. Similar effects arise also in the case of other ion-selective electrodes, in the case of which glass is applied as sensitive material (e.g. thus in the case of Na selective glasses).
Pharmaceutical, chemical, biological, biochemical or biotech processes are, in increasing measure, performed in single-use containers serving as the process container (these are referred to as ‘disposables’, or disposable bioreactors). Such single-use containers can include, for example, flexible containers, e.g. bags, hoses or fermenters, or bioreactors. Bioreactors or fermenters frequently have supply and drain lines, which can be embodied, for example, as hoses or flexible tubes. Inserted in the supply and drain lines can also be rigid tubular pieces or pipes. After terminating a process, the single-use containers can be disposed of. In this way, complex cleaning- and sterilization procedures are avoided. Especially through the use of single use-containers, the risk of cross contamination is avoided, and therewith, process safety increased.
The processes performed in the single-use containers operate in a closed system, i.e. without connection to the environment outside of the single-use container. Since, frequently, sterile conditions are required, the single-use containers must be sterilized before introduction of the process media. To this end, in biochemical, biological, biotechnological and pharmaceutical applications, frequently gamma- or beta radiation is used. Also, while the processes are running in a single-use container, the penetration of impurities, especially of germs, from the environment into the interior of the process container must be prevented, in order not to degrade, or corrupt, the process.
Potentiometric sensors to be used in such a single-use containers can ideally be installed fixedly in a wall of the container already before the sterilization of the container and remain there for the duration of both storage and later use. Such sensors, or containers with such sensors, are described, for example, in German patent application DE 10 2010 063031 A1. While the actual time of use of the single-use container amounts, as a rule, only to a few days up to a number of weeks, storage times of the container with the already installed sensors can be in the order of magnitude of one or more years. Dry storage of the sensor installed in the container brings about, according to the state of the art, the already described disadvantages of lengthened response time. Storage of the sensor in a liquid during sterilization or during a warehousing period is cumbersome and even impractical.
Known from WO 2009/059645 A1 is, for example, a single-use container with integrated pH-sensor, which can also be sterilized together. The pH-sensitive membrane is stored in a compartment containing a pH-stable, storage solution. The storage solution serves also as calibration solution for a one point calibration. For performing measurements, the compartment is opened to the process container in manner not described in greater detail.
Optical, or optochemical, sensors for single use measurements are likewise known.
Also, known from DE 10 2010 001 779 A1 is a calibratable sensor unit for a single use, reaction container, in which case the sensitive element is stored with calibration means, e.g. a buffer solution, before start-up within a compartment closed from the process container by a membrane. Disadvantageous in this embodiment is that the flexible isolating membrane can be damaged during transport or during storage of the reaction container.